Project summary/Abstract Autism is one of the most common neurodevelopmental disorders with a prevalence of ~40- 60 in 10,000 in children in the US (5, 11). Both genes and environmental factors contribute to this complex disorder (13) with recent research suggesting a stronger role for environmental factors (14). However, the role of environment remains elusive even though the public is very concerned. Population-based research applying valid and reliable exposure assessment methods is thoroughly needed. Here, we propose to examine the hypothesis that exposure to specific pesticides during vulnerable periods, particularly during fetal development, determines risks of subsequent development of autistic disorder (AD). California is an excellent location for studying potential environmental contributions to AD. The California Department of Developmental Services (CA-DDS) operates a statewide system of regional centers for autism services and maintains electronic records for all clients. California ranks 1st among US states in agricultural production, with 1/4 of total agricultural pesticide use in the US (15, 16), and is the only state which maintains a statewide pesticide use reporting system. Building onto this unique resource, our group has over 15 years of experience studying health effects from pesticides in California. Previously, we developed a geographic pesticide exposure assessment tool (GRAPES) that utilizes the unique California Pesticide Use Report system, in combination with agricultural land-use maps, to derive record-based estimates of historical residential exposures (17, 18), allowing us to capture month/trimester specific agricultural pesticide exposures statewide. Statewide, we expect to identify >20,000 autism cases with diagnoses up to the age of 72 months from the CA-DDS database born in CA 1997-2009 and >1,700 from agricultural areas as well as 1:10 age-sex match controls from birth records (51). This will provide the largest cohort ever to address hypotheses that exposures to specific chemicals (e.g. neurotoxic or endocrine disrupting agents) contribute to AD during vulnerable periods of development. Specifically, we will examine whether AD is associated with peri-conceptional and fetal exposures to specific pesticides, focusing neurodevelopmental toxins as well as high volume use pesticides; applying sophisticated record based exposure assessment techniques to determine pesticide exposures while avoiding recall bias due to over-reporting of exposures among case parents. We have available the to-date most refined, state-of-the-art objective pesticide assessment tool that provides us with individual level exposures during an extended observation period, in a large area and for a large population (the state of California). Improving our understanding of impacts of environmental toxins will inform environmental health policy on pesticide regulation, advance primary prevention of autism, and potentially provide scientific insights into biologic mechanisms of autism development.